A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous and Subcutaneous RO7121932 Administration in Participants With Multiple Sclerosis

Официальное название

A Multiple-center, Non-randomized, Open-label, Adaptive, Single-ascending Dose (Part 1 and Part 2) and Multiple-ascending Dose (Part 3) Parallel, Phase IB Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of RO7121932 Following Intravenous (Parts 1) and Subcutaneous Administration (Parts 2 and 3) in Participants With Multiple Sclerosis

Обзор

The primary purpose of the study is to evaluate the safety and tolerability of a single-ascending intravenous (IV) dose (Part 1), a single-ascending subcutaneous (SC) dose (Part 2), and multiple ascending SC doses (Part 3) of RO7121932 in participants with multiple sclerosis (MS).

Вмешательства

• Препарат RO7121932 IV
  Participants will receive RO7121932, as an IV infusion, per the schedule specified in the treatment arms.
• Препарат RO7121932 SC
  Participants will receive RO7121932, as SC injection, per the schedule specified in the treatment arms.

Первичные конечные точки

• Parts 1, 2, and 3: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) With Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE V5) [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3]
• Parts 1, 2, and 3: Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Day 1 to Day 197 for Part 3]
• Parts 2 and 3: Percentage of Participants With Local Pain at the Site of Injection Assessed Using the Visual Analog Scale (VAS) [Срок оценки: Day 1, 2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3]
• Parts 2 and 3: Percentage of Participants With Local Injection-site Reaction Using Local Injection-site Symptom Assessment (LISSA) [Срок оценки: Day 1,2, 5, 8 for Part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for Part 3]

Вторичные конечные точки (12)

• Parts 1, 2 and 3 (Week 1 and Week 4): Time to Maximum Observed Concentration (Tmax) of RO7121932 [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3]
• Parts 1, 2 and 3 (Week 1 and Week 4): Maximum Observed Serum Concentration (Cmax) of RO7121932 [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Days 1, 2, 5 and, 22 for Part 3]
• Parts 1, 2 and 3 (Week 1 and Week 4): Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose [Срок оценки: Day 1 (predose) to Day 8 (168 hours post-dose) for Parts 1, 2, and 3 (Week 1) and Day 22 (predose) to Day 29 (168 hours post-dose) for Part 3 (Week 4)]
• Parts 1 and 2: Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2]
• Parts 1 and 2: AUC From Time 0 to Infinity (AUCinf) [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2]
• Part 1: Total Body Clearance (CL) Of RO7121932 [Срок оценки: Day 1 to Day 169]
• Parts 2 and 3 (Week 4): Apparent Clearance (CL/F) of RO7121932 [Срок оценки: Day 1 to Day 169 for Part 2; Day 22 to Day 29 for Part 3]
• Parts 1, 2 and 3: Terminal Rate Constant of RO7121932 [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3]
• Parts 1, 2 and 3: Apparent Terminal Half-Life (T1/2) of RO7121932 [Срок оценки: Day 1 to Day 169 for Part 1 and Part 2; Day 22 to Day 197 for Part 3]
• Part 3: Trough Concentrations (Ctrough) of RO7121932 [Срок оценки: Day 1 to Day 197]
• Part 3 (Week 1 and Week 4): Area Under the Concentration-time Curve Over One Dosing Interval (AUCtau) of RO7121932 [Срок оценки: Day 1, 2, 5 and 22]
• Parts 1 and 3: Cerebrospinal Fluid (CSF) Concentration of RO7121932 [Срок оценки: Screening, Day 2 to Day 169 for Part 1; Screening, Day 2 to Day 197 for Part 3]

Критерии участия

Критерии включения

• Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening
• Participants with relapsing multiple sclerosis (RMS) or progressive multiple sclerosis (PMS) who fulfil international panel criteria for diagnosis (McDonald 2017 criteria)
• Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up)
• Female participants must practice abstinence or otherwise use contraception

Критерии исключения

• Evidence of clinical disease activity as defined by any clinical relapse within 3 months prior to screening, or by >1 clinical relapse within 12 months prior to screening
• Evidence of magnetic resonance imaging (MRI) activity as defined by the presence of ≥ 1 Gadolinium (Gd)-enhancing T1 lesion in the screening MRI scan or by ≥ 4 new or enlarging T2 lesions in the screening scan as compared to a reference scan
• Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML
• Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism
• Known active or uncontrolled bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6 weeks prior to Day 1
• Participants with a current diagnosis of epilepsy
• Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases
• History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening. Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy >1 year prior to screening is not exclusionary
• Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during course of the study
• History of currently active primary or secondary (non-drug-related) immunodeficiency
• History of hypersensitivity to biologic agents or any of the excipients in the formulation
• Only for cohorts where CSF samples are planned to be collected: Participants with a history of spinal cord compression, raised intra-cerebral pressure, clinically significant vertebral joint pathology or any other current abnormalities in the lumbar region which could prevent the lumbar puncture procedure.

Prior/Concomitant Therapy:

• Treatment with any approved MS treatment at Screening. Participants may become eligible after completion of a washout period prior to acquiring any screening laboratory tests but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial
• Previous treatment with RO7121932, alemtuzumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation. For the USA only, previous treatment with daclizumab
• Previous treatment with anti-cluster of differentiation 20 (CD20) B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab)

• <12 months prior to acquiring any screening laboratory tests,
• ≥12 months prior to acquiring any screening laboratory tests, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available),
• If discontinuation of a prior B-cell depletion therapy was motivated by safety reasons
• Current or prior treatment with natalizumab (if <24 months prior to acquiring any screening laboratory tests)

Prior/Concurrent Clinical Study Experience:

\- Participation in an investigational drug medicinal product or medical device study within 30 days before Screening or within five times the pharmacodynamic (PD) or pharmacokinetic (PK) half-life (if known), whichever is longer

Diagnostic Assessments:

• Positive result on human immunodeficiency virus (HIV1) and HIV2, hepatitis C, or hepatitis B
• Participants with SI or behavior within 6 months prior to Screening or participants who, in the Investigator's judgment, pose a suicidal or homicidal risk
• Vaccination with a live or live-attenuated vaccine within 6 weeks prior to Day 1

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 6 центров

• Universitätsklinikum "Carl Gustav Carus" — Dresden
• Universitätsmedizin Göttingen Georg-August-Universität — Göttingen
• Klinikum rechts der Isar der TU Muenchen — München
• Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie — Münster
• Universitätsklinikum Tübingen, Zentrum für Neurologie — Tübingen
• Universitätsklinikum Ulm — Ulm

Польша · 6 центров

• Uniwersyteckie Centrum Kliniczne — Gda?sk
• Regionalny Szpital Specjalistyczny im. W. Bieganskiego — Grudzi?dz
• MedPolonia — Poznan
• Osrodek Badan Klinicznych Euromedis — Szczecin
• Instytut Psychiatrii i Neurologii II Klinika Neurologiczna — Warsaw
• SPSK nr 1 — Zabrze

США · 5 центров

• Stanford University Medical Center — Stanford
• Yale University Multiple Sclerosis Center — New Haven
• University of South Florida — Tampa
• University of Massachusetts Medical School — Worcester
• UC Health, LLC. — Cincinnati

Португалия · 3 центра

• Hospital de Braga — Braga
• Hospital Santo Antonio dos Capuchos — Lisbon
• Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião — Santa Maria da Feira

Бельгия · 2 центра

• Cliniques Universitaires St-Luc — Brussels
• UZ Gent — Ghent

Израиль · 2 центра

• Hadassah University Hospital - Ein Kerem — Jerusalem
• Tel Aviv Sourasky Medical Center — Tel Aviv

Италия · 2 центра

• IRCCS Ospedale San Raffaele — Milan
• Fond. Istituto Neurologico C.Besta — Milan

Румыния · 2 центра

• ARENSIA Exploratory Medicine SRL - Bucharest (Monza Medical Center) — Bucharest
• ARENSIA Exploratory Medicine, County Emergency Hospital — Cluj-Napoca

Канада · 1 центр

• Montreal Neurological Institute and Hospital — Montreal

Moldova · 1 центр

• ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital — Chisinau

Сербия · 1 центр

• University Clinical Center of Serbia — Belgrade

Испания · 1 центр

• Hospital Universitari Vall dHebron (CEMCAT) — Barcelona

Идентификаторы

NCT: NCT05704361 · BP42230 · 2020-004122-33 · 2023-509357-31-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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